The present invention is generally in the field of magnetic separation techniques and relates to a system for the correction of a biological fluid, such as blood, lymph and spinal fluid.
Methods of blood correction are known and widely used in particular for treatment in patients suffering from kidney and/or liver diseases. One of the conventional techniques, known as haemo- or lymph-perfusion, is based on passing blood or lymph fluid through an adsorbent such as granular activated carbon. Unfortunately, a relatively large amount of biological fluid, namely about 250-300 ml needs to be withdrawn from the patient""s body at any given time, and the entire system is cumbersome. Furthermore, the carbon loses its effectiveness after 15-20 minutes from the beginning of the treatment because it slimes and, owing to the relatively large dimensions of the carbon particles, becomes formed with numerous channels formed therein by the blood passage therethrough. As a result, unpurified blood returns into the body.
Another conventional technique, known as haemodialysis, is based on the use of semipermeable membranes. Similarly to the haemoperfusion, this method also requires the withdrawal of about 400-600 ml of blood at any given time. The whole process of purification requires blood to circulate through the apparatus more than 5 times. Both of the above described techniques disturb the blood""s rheology. That is to say they traumatize the erythrocytes and thrombocytcs. They also require bulky equipment.
Methods and devices for blood purification have been developed employing the so called haemoseparation technique which is based on the principles of magnetic separation. Generally, the magnetic separation procedure consists of retaining magnetic materials in a chamber disposed in a magnetic field. Systems of this kind typically provide mixing of the blood with a previously prepared magneto-conductive substance formed of paramagnetic beads having a coating which selectively binds a preselected pathogenic agent or endotoxin. Then, by passing a blood mixture containing the paramagnetic beads having the bound pathogenic agent through a magnetic field, the paramagnetic beads are magnetically separated from the blood.
U.S. Pat. No. 5,123,901 discloses a method and an apparatus for removing preselected cells or viruses from the blood. The blood is first tested for selecting a preselected pathogenic agent and identifying an associated antigenic agent. A composition is then prepared, such as an immunoglobulin or an antibody, for coating a plurality of paramagnetic beads with outer layers so as to recognize and bind selectively to the preselected pathogenic agent. The paramagnetic beads have a smooth surface in order to minimize the amount of antibody necessary to coat the beads. The blood is perfused into a flow line, and the coated paramagnetic beads are metered into the blood either before its entering a mixing coil, or thereafter. A received mixture of blood and paramagnetic beads/pathogenic agent complexes flows into a chamber of a magnetic separator. A graded magnetic field is provided along the length of the separation chamber, so as to adhere substantially all of the paramagnetic beads/pathogenic agent complexes to the separation chamber wall. However, both the mixing chamber and the separation chamber are bulky, namely each about 300 cm in length. About 600 to 700 ml of blood occupies the flow circuit at any given time, while the purging process is completed in approximately 6 to 10 hours of operation. Additionally, the magnetic field is graded such that it begins at 4000 Gauss (0.4 T) and increases to about 10000 Gauss (1 T), which is too much for such a biological fluid as blood. Indeed, it is known in the art that the magnetic field intensity which is suitable for intervention into a biological fluid is defined by the properties of the latter. This is more essential for such a multicomponent biological fluid as blood containing ethrocytes whose equidistance increases and membrane resistivity decreases with the increase of the magnetic field. As a result, the erythrocytes grow old and break.
PCT Publication No. WO 94/21310 discloses a method and an apparatus for correcting a biological fluid typically based on mixing the latter with a biocompatible suspension of a magneto-conductive composition within a mixing chamber, and, then, passing the obtained mixture through a filter disposed within a magnetic field. The biological fluid is corrected in a number of cycles. In order to provide more effective mixing, the mixing chamber is filled in with discrete doses of the biological fluid and the suspension of the magneto-conductive composition. The obtained mixture is left standing whilst being continuously mixed, and, then, each further dose is added to the previously obtained mixture. The resulting mixture than passes through a filter disposed in a magnetic field effect region. The time of passage of the mixture through the filter is preset so as to achieve an optimum effect in the magnetic field which does not exceed 120 mT. Unfortunately, such procedure is slow, requiring that about 100 ml of the biological fluid be withdrawn from the body during a cycle and resulting in about 10 hours of operation for the complete correction of the total amount of the patient""s blood.
It should be noted that such parameters as the amount of biological fluid which is withdrawn from the patient""s body at any given time and the duration of the whole treatment are very important and even determinant when dealing with endotoxic and/or exotoxic shocks which are usually caused by poisoning.
There is accordingly a need in the art to facilitate the purification of a biological fluid by providing a novel magnetic system for correcting a biological fluid, such as blood, lymph or spinal fluid, by removing therefrom various endotoxins and exotoxins.
It is a major feature of the present invention to provide such a device which is miniature and easy to construct, and requires a very small amount of biological fluid to be withdrawn from the patient""s body.
There is thus provided according to a broad aspect of the present invention a system for correcting a patient""s biological fluid containing various low-, medium- and high-molecular toxins, the system comprising:
(i) an outlet means for attaching to the patient""s body for substantially continuously withdrawing therefrom the biological fluid containing the various toxins;
(ii) an inlet means for attaching to the patient""s body for returning corrected biological fluid back into the patient""s body;
(iii) an extracorporeal flow line interconnected between the outlet and inlet means for passing therethrough, in a substantially continuous flow, a predetermined amount of the biological fluid substantially not exceeding 100 ml, so as to be mixed with a plurality of magneto-conductive particles capable of adsorbing said toxins for obtaining a mixture of the biological fluid with said particles;
(iv) a magnetic mechanism comprising a magnetic field source producing a magnetic field region within a flow of said mixture for retaining said magneto-conductive particles in said region from a flow of particle-free biological fluid to be returned into the patient""s body through the inlet means.
Preferably, the flow line is in the form of a flexible tube.
The magneto-conductive particles may be contained in a vessel coupled to the flow line through a pipe. To this end, the system comprises a feeding means for substantially continuously feeding the particles into and through the flow line. Preferably, the feeding means comprises a pump coupled to the vessel for supplying air thereto so as to provide an excessive pressure within the vessel.
Additionally, the system may also comprise a feeding means (e.g., a pump) for substantially continuously feeding the biological fluid containing various toxins into and through the flow line. The same pump, which may be of a peristaltic or piezoelectric type, may be employed for feeding both the magneto-conductive particles and the biological fluid.
Alternatively, the magneto-conductive particles may be located inside the flow line in a flow path of the biological fluid containing the various toxins. The flow line may include first and second flexible tubes and a sealed vessel. The magneto-conductive particles are accommodated within a bottom region of the vessel. The first tube is connected between the outlet means and the particles, while the second tube is connected between the inlet means and a top region of the vessel.
Preferably, the particles are contained in a suspension thereof. The suspension may be formed of either a blood substitute composition, physiological solution or the like allowed for intravenous injection.
If the biological fluid is blood, the outlet and inlet means are associated with the patient""s artery and vein, or with two locations on his vein. If the biological fluid to be corrected is the patient""s lymph, the outlet means includes a catheter implanted into the large pectoral lympheduct at the place of its falling into the cava, and the input means includes a catheter inserted into either jugular or cubital vein. If the patient""s spinal fluid is to be corrected, the outlet means includes a needle inserted into the cistern through the cervical opening, and the inlet means includes a needle inserted between the 4th and the 5th lumbar vertebrae. Alternatively, a two-channel needle, installed either into the cistern through the cervical opening or into the spine between the 4th and the 5th lumbar vertebrae, can be used
The magneto-conductive particles are formed of paramagnetic or ferromagnetic material, and may have prevailing hydrophilic or hydrophobic properties.
The system, preferably, also comprises a mixing means located in the flow path of the biological fluid containing the various toxins. The suing means may comprise a multi-threaded worm mechanism. Alternatively, the mixing means may comprise a magnetic mechanism having displaceable opposite magnetic poles.
The magnetic field source comprises at least one permanent magnet mounted outside the flow line and proximate thereto. The permanent magnet may be in the form of a substantially flat plate, or a ring surrounding the flow line. The opposite poles of the magnet may be connected by a cover plate formed of a magnetic soft material.
The magnetic mechanism may also comprise a wire wound on the outer surface of the flow line wit the magnetic field region. Additionally, or alternatively, the magnetic mechanism may comprise an adhering means accommodated inside the flow line for adhering thereon the magneto-conductive particles. Such an adhering means may be a paramagnetic or ferromagnetic filler element installed inside the flow line within the magnetic field effect region. The filler may be in the form of a loosely laid wire, e.g., a barbed wire. The wire may have a varying diameter and a varying laying density along the magnetic field region. It should be noted that the magnetic field source and the adhering means may be constituted by at least one permanent magnet accommodated inside the flow line.
The system also comprises a control means coupled to the flow line and to the magnetic mechanism for operating the same. Preferably, the control means includes a plurality of clamps accommodated along the flow line for regulating the flow of the biological fluid and a monitoring means for checking velocities of the flow of the biological fluid containing the various toxins, the mixture and the particle-free biological fluid.
If the biological fluid to be corrected is the patient""s blood, the system preferably also comprises a filtering means for removing water from blood which may include at least one semipermeable membrane, or water adsorbent material formed of hydrolyzed starch polymer. The filtering means may be accommodated either in the flow path of blood containing the various toxins, or in the flow path of the particle-free blood. The magneto-conductive particles are formed with activated porous surfaces. The particles may be formed of iron, iron oxide, carbon coated iron, silicone coated iron, aluminum coated iron, dextran coated iron. Preferably, the magneto-conductive particles are further coated with a protective layer formed of protein or the patient""s blood.
The advantages of the present invention are thus self-evident. The system according to the invention needs a very small amount of the biological fluid to be withdrawn from the patient""s body at a given time. This is very important feature, because it, on the one hand, does not cause danger to the patient and, on the other hand, enables to make the system desirably miniature.